Possible Mechanism Responsible for Mechanical Dysfunction of Ischemic Myocardium: A role of Oxygen Free Radicals : SYMPOSIUM ON PROTECTION OF ISCHEMIC MYOCARDIUM : Basic and Clinical Research
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概要
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It has been proposed that a major target organelles damaged by the ischemic process, probably by the oxygen free radicals generated, is the portion of the excitation-contraction coupling system that regulates Ca^<2+> delivery (the sarcoplasmic reticulum and sarcolemma) to the contractile proteins. We tested this hypothesis by studying the effect of in vitro generation of oxygen free radicals from xanthine-xanthine oxidase system or dihydroxyfumarate (DHF)/Fe^<3+>-ADP system on Ca^<2+> flux behavior of canine cardiac sarcoplasmic reticulum (SR); sarcolemmal (Na^+, K^+)-ATPase activity. Generation of oxygen free radicals by xanthine oxidase acting on xanthine as a substrate increased the passive Ca^<2+> effiux and decreased intravesicular Ca^<2+> with no effect on active Ca^<2+> influx (Ca^<2+>-ATPase of SR vesicles. Similar exposure of sarcolemmal vesicles to xanthine plus xanthine oxidase stimulated Na^+-Ca^<2+> exchange activity. When sarcolemmal vesicles were incubated with DHF plus Fe^<3+>-ADP, (Na^+, K^+)-ATPase activity was decreased. It is postulated that the SR Ca^<2+> efflux pathways but not catalytic activity of the Ca^<2+> pump and sarcolemmal (Na^+, K^+)-ATPase involving Na^+-Ca^<2+> exchange activity are altered by oxygen free radicals, and such changes may partly account for the occurrence of intracellular Ca^<2+> overload during the course of myocardial ischemia. Interestingly, oxygen free radicals from xanthine-xanthine oxidase system had no effect on myofibrillar pCa-ATPase curve. From this set of observations we would hypothesize that the SR and sarcolemma may be the principal target organelles of oxygen free radicals attack in the ischemic injury and not the contractile proteins per se.
- 社団法人日本循環器学会の論文
- 1989-09-20
著者
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ITO HARUO
Department of Urology, Chiba University
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OKABE Eiichiro
Department of Pharmacology and ESR Laboratory, Kanagawa Dental College
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Murayama Masahiro
The 2nd Department of Internal Medicine, St. Marianna University School of Medicine
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Okabe Eiichiro
Deparment Of Pharmacology Kanagawa Dental College
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Ito Haruo
Department Of Pharmacology Kanagawa Dental College
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Murayama Masahiro
The 2nd Department Of Internal Medicine St.marianna University School Of Medicine
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FUJIMAKI RIKIYA
The 2nd Department of Internal Medicine, St.Marianna University School of Medicine
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Fujimaki Rikiya
The 2nd Department Of Internal Medicine St.marianna University School Of Medicine
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Murayama Masahiro
The 2nd Department Of Institute Medicine St. Marianna University School Of Medicine
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